The present disclosure relates to devices for repairing or regenerating a meniscus or a portion of a meniscus in a knee.
It is known to use various collageneous scaffolds to provide a matrix for repair and regeneration of damaged tissue. U.S. Pat. No. 6,042,610 to ReGen Biologics, hereby incorporated by reference, discloses the use of a device comprising a bioabsorbable material made at least in part from purified natural fibers of collagen or glycosaminoglycans. The purified natural fibers are cross-linked to form the device of U.S. Pat. No. 6,042,610. The device can be used to provide augmentation for a damaged meniscus. Related U.S. Pat. Nos. 5,735,903, 5,681,353, 5,306,311, 5,007,934, and 4,880,429 also disclose a meniscal augmentation device for establishing a scaffold adapted for ingrowth of meniscal fibrochondrocyts.
It is also known to use naturally occurring extracellular matrices (ECMs) to provide a scaffold for tissue repair and regeneration. One such ECM is small intestine submucosa (SIS). SIS has been described as a natural biomaterial used to repair, support, and stabilize a wide variety of anatomical defects and traumatic injuries. See, for example, Cook® Online New Release provided by Cook Biotech of Bloomington, Ind., a copy of which can be found at their online website. The SIS material is reported to be a naturally-occurring collagenous matrix derived from porcine small intestinal submucosa that models the qualities of its host when implanted in human soft tissues. Further, it is taught that the SIS material provides a natural matrix with a three-dimensional structure and biochemical composition that attracts host cells and supports tissue remodeling. SIS products, such as Oasis material and Surgisis material, are commercially available from Cook Biotech, Bloomington, IN.
An SIS product referred to as RESTORE Orthobiologic Implant is available from DePuy Orthopaedics, Inc. in Warsaw, Ind. The DePuy product is described for use during rotator cuff surgery, and is provided as a resorbable framework that allows the rotator cuff tendon to regenerate itself. The RESTORE Implant is derived from porcine small intestine submucosa that has been cleaned, disinfected, and sterilized. Small intestine submucosa (SIS) has been described as a naturally-occurring ECM composed primarily of collagenous proteins. Other biological molecules, such as growth factors, glycosaminoglycans, etc., have also been identified in SIS. See Hodde et al., Tissue Eng. 2(3): 209-217 (1996); Voytik-Harbin et al., J. Cell Biochem., 67:478-491 (1997); McPherson and Badylak, Tissue Eng., 4(1): 75-83 (1998); Hodde et al., Endothelium, 8(1):11-24 (2001); Hodde and Hiles, Wounds, 13(5): 195-201 (2001); Hurst and Bonner, J. Biomater. Sci. Polym. Ed., 12(11) 1267-1279 (2001); Hodde et al., Biomaterial, 23(8): 1841-1848 (2002); and Hodde, Tissue Eng., 8(2): 295-308 (2002), all of which are incorporated by reference herein. During seven years of preclinical testing in animals, there were no incidences of infection transmission from the implant to the host, and the SIS material has not decreased the systemic activity of the immune system. See Allman et al., Transplant, 17(11): 1631-1640 (2001); Allman et al., Tissue Eng., 8(1): 53-62 (2002).
Other products made from porcine small intestine are commercially available. For example, Organogenesis, Inc., of Canton, Mass., is understood to market such products under the designations GRAFTPATCH, FORTAFLEX, FORTAGEN and FORTAPERM, and possibly under other designations.
While small intestine submucosa is available, other sources of submucosa are known to be effective for tissue remodeling. These sources include, but are not limited to, stomach, bladder, alimentary, respiratory, or genital submucosa, or liver basement membrane. See, e.g., U.S. Pat. Nos. 6,171,344, 6,099,567, and 5,554,389, hereby incorporated by reference. Further, while SIS is most often porcine derived, it is known that these various submucosa materials may be derived from non-porcine sources, including bovine and ovine sources. Additionally, other collageneous matrices are known, for example lamina propria and stratum compactum.
For the purposes of this disclosure, it is within the definition of a naturally occurring ECM to clean, delaminate, and/or comminute the ECM, or even to cross-link the collagen fibers within the ECM. It is also within the definition of naturally occurring ECM to fully or partially remove one or more sub-components of the naturally occurring ECM. However, it is not within the definition of a naturally occurring ECM to extract and purify the natural collagen or other components or sub-components of the ECM and reform a matrix material from the purified natural collagen or other components or sub-components of the ECM. Thus, while reference is made to SIS, it is understood that other naturally occurring ECMs are within the scope of this invention. Thus, in this application, the terms “naturally occurring extracellular matrix” or “naturally occurring ECM” are intended to refer to extracellular matrix material that has been cleaned, disinfected, sterilized, and optionally cross-linked. The terms “naturally occurring extracellular matrix” and “naturally occurring ECM” are also intended to include ECM foam material prepared as described in copending U.S. patent application Ser. No. 10/195,354 entitled “Porous Extracellular Matrix Scaffold and Method”, filed concurrently herewith.
The following patents, hereby incorporated by reference, disclose the use of ECMs for the regeneration and repair of various tissues: U.S. Pat. Nos. 6,334,872, 6,187,039, 6,176,880, 6,126,686, 6,099,567, 6,096,347, 5,997,575, 5,993,844, 5,968,096, 5,955,110, 5,922,028, 5,885,619, 5,788,625, 5,762,966, 5,755,791, 5,753,267, 5,733,337, 5,711,969, 5,645,860, 5,641,518, 5,554,389, 5,516,533, 5,460,962, 5,445,833, 5,372,821, 5,352,463, 5,281,422, and 5,275,826. U.S. Pat. Nos. 5,275,826 and 5,516,533 disclose providing a mass of SIS, particularly as a fluidized injectable mass, to promote repair of tissue defects. U.S. Pat. No. 5,352,463 discloses an SIS pillow filled with comminuted SIS for regeneration of a meniscus. While U.S. Pat. No. 5,352,463 contemplates the general concept of meniscus regeneration with an SIS filled pouch, it does not address itself to providing such a pouch having the capability of withstanding the compression and shear stresses involved in an implant for regenerating a meniscus.
The present disclosure relates to a device for regenerating a meniscus of a knee or a portion thereof. A natural meniscus in a human knee has a generally wedge-shaped cross-section, i.e., a section through a plane extending along and radially outwardly from the axis of the tibia either through the medial meniscus or the lateral meniscus will define a generally wedged-shaped cross-section. Typically, the device will be placed in a meniscal space from which a defective portion of the meniscus is removed, and that space will be a generally wedge-shaped space. The device will be placed in the space and anchored to the surrounding tissue. In one embodiment, a composite device will be inserted into the space from which the defective meniscus portion has been removed. The device comprises an upper cover made from toughened naturally occurring extracellular matrix (ECM), the cover defining a space therebelow. In some embodiments, the cover comprises a plurality of layers of naturally occurring ECM laminated together and toughened to withstand articulation stresses. A mass comprising comminuted naturally occurring ECM is disposed in the space. In various embodiments, the mass may also comprise bioactive agents, biologically-derived agents, cells, biological lubricants, biocompatible inorganic materials, biocompatible polymers and/or some combination thereof mixed with the comminuted ECM.
In some embodiments, a biocompatible polymer can be used in conjunction with naturally occurring ECM. See, for example, the teachings of U.S. patent application Ser. No. 10/195,341 entitled “Hybrid Biologic/Synthetic Porous Extracellular Matrix Scaffolds” filed contemporaneously herewith, and U.S. patent application Ser. No. 10/172,347 entitled “Hybrid Biologic-Synthetic Bioabsorbable Scaffolds,” which was filed on Jun. 14, 2002.
An implant for regeneration or repair of the meniscus of the knee may be toughened to withstand better the compression and/or shear forces of the knee for a sufficient amount of time for remodeling to begin. It will be understood that a surgeon may immobilize or partially immobilize the knee for a period of time subsequent to surgery. The rehabilitation protocol may include limited articulation, compression, and shear forces for a period of time. However, an implant that is toughened should be able to withstand even these reduced forces better than an equivalent implant that has not been toughened. At the same time, the material must be porous enough to permit remodeling. Thus, it is preferred that the condyle-facing surface of the ECM device of this disclosure is toughened to withstand the forces. Toughness may include stiffness (i.e. tensile modulus), resistance to delamination, increased thickness, resistance to shear or abrasion, decreased water content, or increased density, for example.
One method of toughening is dehydrothermal cross-linking. Techniques for dehydrothermal cross-linking are known in the art, but the steps in one method include applying mechanical pressure to the ECM while using vacuum to remove water, and subsequently delivering pressurized warm air to the ECM, thus producing a dehydrated ECM. Other methods of mechanical cross-linking, as are known in the art, may be used to toughen the upper cover of the device of the present disclosure. Such methods of physical cross-linking include, for example, freeze-drying, irradiation (ultraviolet or gamma irradiation) and combinations of methods. In addition, chemical cross-linking can be used to toughen the upper cover of the device of the present disclosure. Chemical cross-linking can be achieved through the use of materials like aldehydes, carbodiimides, glycation agents, enzymes and the like.
In some embodiments, the upper cover is formed by laminating a plurality of sheets of naturally occurring ECM and treating it to provide a toughened surface capable of withstanding the compression and shear stresses involved in knee articulation, i.e., the articulation of the knee condyle on the device inserted into the meniscus. The mass in the space below the upper cover may be comminuted SIS or is alternatively bioactive agents, biologically derived agents, cells or combinations thereof, for example. Other collageneous materials may also be used for the mass in the space below the upper cover, alone or in combination with the above-mentioned materials. The mass of comminuted naturally occurring ECM is believed to provide a framework for meniscus regeneration. The insertion of the device into the space from which the defective portion has been removed and the attachment of the device to the surrounding tissue places the device such that it is in contact with the host tissue of the remaining meniscus such that the meniscus will be regenerated in the space from which the defective portion is removed. However, in some embodiments the space below the upper cover is left empty; if desired, biological material may be implanted as a discrete element or could be injected intraoperatively or post-operatively for example.
To reduce the stress on the upper surface of the device, a lubricant may be affixed or applied to the toughened surface of the implant. For example, a lubricant such as hyaluronic acid may be affixed to the upper surface of the device by cross-linking. Other lubricants can also be used. Reference is made to U.S. patent application Ser. No. 10/195,606 entitled “Cartilage Repair and Regeneration Device and Method”, filed concurrently herewith, which is incorporated by reference herein in its entirety.
One embodiment, therefore, is a composite device comprising a cover of naturally occurring ECM and a framework therebelow provided to accommodate the regeneration. With the mass of comminuted ECM, the device serves as a cushion for the condyle load and a bearing surface for the condyle. By placing the device into close contact with the remaining portion of the meniscus, the regeneration will take place.
In another embodiment of the present invention, the device comprises a shell shaped conformingly to fit into the space occupied by the removed meniscus portion, the shell to provide an upper surface to withstand the articulation of the knee and a space below the upper surface. A bioactive agent, biologically derived agent, cells, biocompatible polymer, biocompatible inorganic material, biological lubricant or combinations thereof is disposed within the space. It will be appreciated that shells of different size and shape will be provided to surgeons such that they can remove a portion of the damaged meniscus conforming to the shape of a device to be inserted or size the shell to conform to the removed portion of damaged meniscus. Templates can be provided to guide the surgeon in the removal of the defective portion. Preferably, the device is shaped to conform to the space into which it is inserted such that the surrounding tissue of the remaining meniscus is in contact with the device. It has been found, for example, that a plug made from comminuted ECM such as SIS may be inserted into a hole in a meniscus to regenerate the meniscus and close the hole. Such a plug may be wrapped or covered with layers of SIS.
For handling purposes, the devices will preferably be made in a factory and supplied to the surgeons for selection and use based on size and shape. In some embodiments, the devices will be provided in dried or lyophilized condition to be hydrated by the surgeon. Portions of the exterior of the device, particularly those portions providing communication with the biological mass under the upper cover, may be perforated to expedite the hydration of the device.
In some embodiments, the device for regenerating a meniscus or a portion thereof comprises a wedge-shaped biological scaffold material body having an apex portion and a base portion spaced radially outwardly from the apex portion. The body provides an upper surface to face a condyle of the femur and to provide for articulation of the knee against the upper surface and a lower surface to face the tibial platform of the knee. This body, which may be fabricated from sheets or strips of naturally occurring ECM, is formed to provide a plurality of channels or compartments disposed between the upper and lower surfaces. In some embodiments, the channels or compartments extend radially inwardly from the base portion to the apex portion. In other embodiments, the channels or compartments extend circumferentially about the device, i.e., in the circumferential direction of the original meniscus. In some embodiments, the radially extending channels will be generally conical in shape with their large ends disposed toward the base portion and their smaller ends disposed toward the apex portion. In some embodiments, the circumferential channels will be arranged such that smaller diameter channels will be disposed toward the apex portion and larger diameter channels will be disposed adjacent the base portion.
These channels or compartments may be filled with comminuted naturally occurring ECMs to provide a framework for meniscus regeneration. In some embodiments, the comminuted ECM will be mixed with or replaced by bioactive agents, biologically-derived agents, cells, biological lubricants, biocompatible inorganic materials, biocompatible polymers and/or combinations thereof. The ECM material providing the upper surface and the lower surface may be laminated sheets or strips of an ECM material such as SIS which may be formed under pressure and heat. It will be appreciated that lyophilization may be used to dry the mass of comminuted material.
It will be appreciated that various structures may be provided within the concept of the present disclosure to produce a composite device having an upper cover made from a toughened sheet of a naturally occurring ECM with a mass of comminuted naturally occurring ECM therebelow to accommodate the regeneration of the meniscus. For example, a device for regenerating a meniscus or a portion thereof may comprise a wedge-shaped body having radially extending or circumferentially extending compartments or channels into which the comminuted ECM is placed. The upper or lower panels may merely serve as covers for the device's internal structure which may be made separately from the panels as will be further described herein. In some embodiments, the devices are made in the shape of a pillow, the upper and lower covers of which provide an interior space which is filled with a biological material to provide a framework for meniscus regeneration. Channels or compartments within the space between the upper and lower covers may be fabricated, for example, with partitions of ECM material to direct the regeneration. In some cases, the channels or compartments will extend radially inwardly and in other cases, the channels or compartments will extend circumferentially.
Various systems may be provided for forming naturally occurring ECMs such as SIS layers or strips to provide the panels or covers and to provide the recesses, channels or compartments in between the panels or covers. It has been found that layers of harvested and cleaned SIS may be drawn into cavities in vacuum forming operations. Such layers of SIS may be formed and then laminated together and dried by the application of heat and pressure. The mass of biological material such as the comminuted SIS may be placed in the vacuum formed cavities as part of the forming process.
The present invention also comprises a method of regenerating a portion of a knee meniscus comprising the steps of removing a segment of a meniscus to provide a partial meniscal space extending circumferentially about a predetermined portion of the tibial platform and leaving remaining segments of the original meniscus. This partial meniscal space will have a radially outer portion and a radially inner portion. The method involves providing an implant device constructed from naturally occurring ECMs and shaped to conform to the partial meniscal space. The device is placed into the space and then attached to the adjacent tissue of the knee. The method encourages regeneration from the radially outer portion of the device to the radially inner portion of the device. In embodiments of the present invention, the encouraging step comprises channeling blood flow from the vascular rich outer portion of the meniscus and the device to the radially inner portion of the device. The regeneration is encouraged by structuring the device such that the vascular rich portion of the original meniscus and the adjacent radially outer portion of the original meniscus will work with the device and particularly the mass of biological material under the upper cover of the device to regenerate the meniscal tissue.
In one embodiment, the method of the present invention, therefore, comprises the steps of replacing a portion of the original meniscus with a naturally occurring extracellular matrix material shaped and formed to provide an upper surface toughened to withstand the compression and shear stress of articulation of the knee and an interior space into which the meniscal regeneration occurs and attaching the material to the surrounding tissue to provide blood flow to the device. In some embodiments, the interior space is filled with a mass of comminuted naturally occurring extracellular matrix material, bioactive agents, biologically-derived agents, cells or various combinations thereof. In some embodiments, the comminuted ECM may be chemically cross-linked by chemical agents such as aldehydes, carbodiamide, glycation agents, enzymes or the like. See, for example, U.S. Pat. No. 6,042,610, already incorporated by reference, at columns 11-12. In some embodiments, the comminuted ECM may be physically cross-linked by heat (thermal cross-linking), radiation (ultraviolet or gamma irradiation), or combinations such as drying at elevated temperatures (dehydrothermal crosslinking). And in some embodiments a lubricating agent may be applied or affixed to the device.
For handling and installation purposes, some embodiments comprise a cover over a recess which is filled with biological materials and constructed to provide a framework for meniscus regeneration. At least the upper cover is formed from a material which will withstand the compression and shear stresses involved in articulation of the femur on the tibia, i.e., of the condyles on the tibia platform. It will be appreciated that this is a dynamic stress situation for the upper cover and, for that matter, for the device attached to the surrounding tissue or anchored in the space from which the defected meniscus portion is removed. This upper cover of the device may be provided by treating layers of ECM with heat and pressure to form a toughened upper surface.
In this specification and in the appended claims, unless expressly limited otherwise, it is intended that “toughened” or “treatment for toughening” shall involve treating ECM such as SIS with various treatment steps including such steps as laminating several layers of ECM strips together and treating the layers with compression and vacuum or heat or combinations of pressure, vacuum, and heat. It is contemplated that such layers may be laminated together and bonded by both mechanical compression and application of vacuum and/or heated air which accomplishes the bonding and also dries the product, leading to a dehydrated product. It has been found that several layers of SIS can be laminated together with heat, vacuum, and pressure to provide a portion of the composite structure. Illustratively, in some embodiments, both the upper cover and the lower cover defining the shell of the device are treated with heat and pressure to remove water from the ECM comprising the shell to produce a shell comprising a dehydrated naturally occurring extracellular matrix. It has been found that various drying conditions affect the toughness of the ECM. For example, changing the platen or drying surface in vacuum drying by reducing the size of the openings in the platen can increase the toughness of the resultant ECM. Drying in air or hot air, as compared to in vacuum, can also produce a dehydrated extracellular matrix having increased toughness. Any method to increase density, for example by increasing the number of layers of ECM in a given volume, will also increase toughness. Altering the orientation of layers, selecting older animals, selecting species having tougher ECMs, and processing techniques (for example, increasing concentration of peracetic acid or pressure from rollers) can also affect the toughness of the resultant ECM.
Unless otherwise expressly limited, “toughened” or “treatment for toughening” may also include other means of cross-linking ECM. As discussed above, the ECM can be chemically crosslinked to increase the toughness of all or a portion of the ECM through the use of agents such as aldehydes, carbodiimides, glycation agents, enzymes and the like. In addition, as discussed above, other methods of crosslinking the ECM may be used. For example, radiation (including UV, RF, and gamma radiation) could be used to toughen the ECM. When UV or RF radiation is used, preferably the ECM is crosslinked prior to final drying. Additionally, combinations of methods may be used, such as be drying at elevated temperatures (dehydrothermal crosslinking). All of such methods are intended to be included in the expressions “toughened” and “treatment for toughening” unless expressly limited.
In this specification and claims, unless expressly limited otherwise, “generally wedge-shaped” is intended to define the shape of a device that has a thick base portion and a thin apex portion, wherein the device tapers between the thick base portion and the thin apex portion. Although a generally wedge-shaped device can have flat upper and lower surfaces (see, e.g., FIG. 12), such a device can also have one or more surfaces that are curved, such as a tapering convex surface (see, e.g. FIG. 49) or a tapering concave surface, or could have stepped or contoured surfaces that follow the contour of any underlying material.
In this specification and claims, unless otherwise expressly limited, “mass of biological material” is intended to include naturally occurring extracellular matrix, bioactive agents, and/or biologically-derived agents and cells. “Mass of biological material” is also intended to include biological materials formed in whole or in part from such matrices, agents and cells. Thus, “mass of biological material” includes comminuted extracellular matrix and extracellular matrix foams as disclosed in U.S. patent application Ser. No. 10/195,354 entitled “Porous Extracellular Matrix Scaffold and Method”, and hybrid materials, as disclosed in U.S. patent application Ser. No. 10/195,341 entitled “Hybrid Biologic/Synthetic Porous Extracellular Matrix Scaffolds”, all of which are filed concurrently herewith, and U.S. patent application Ser. No. 10/172,347 entitled “Hybrid Biologic-Synthetic Bioabsorbable Scaffolds” which was filed on Jun. 14, 2002, the disclosures of which are incorporated by reference herein. Unless otherwise expressly limited, “mass of biological material” includes material from which commercially available products are made, including, for example: the RESTORE® Orthobiologic Implant, available from DePuy Orthopaedics, Inc. of Warsaw, Indiana; OASIS and SURGISIS products available from Cook Biotech, Inc. of Bloomington, Indiana; “TISSUEMEND” available from TEI Biosciences Inc. of Boston, Mass.; and GRAFTPATCH, FORTAFLEX, FORTAGEN and FORTAPERM products available from Organogenesis, Inc. of Canton, Mass. Unless expressly limited otherwise, the expression “mass of biological material” is also intended to encompass purified collagen, such as that disclosed in U.S. Pat. No. 6,042,610. The expression “mass of biological material” is intended to encompass all such materials regardless of whether they include another material, regardless of their physical state (e.g. powder or foam), and regardless of whether they are cross-linked or otherwise toughened, unless otherwise expressly stated. The expression “mass of biological material” should be understood to encompass both materials that are integral and that which comprise discrete elements. “Mass of biological material” should also be understood to encompass all forms of these materials, including dry forms, solutions, dispersions, gels, and pastes for example. Specific examples of materials for the mass of biological materials include: comminuted ECM; ECM pieces; ECM foam; an ECM roll; woven ECM; a non-woven ECM mat; braided ECM; ECM solution; ECM dispersion; ECM slurry; ECM gel; ECM paste; and ECM that has not been toughened. Such ECMs include but are not limited to: comminuted SIS; SIS pieces; SIS foam; an SIS roll; woven SIS; non-woven SIS mat; braided SIS; SIS solution; SIS dispersion; SIS slurry; SIS gel; SIS paste; and SIS that has not been toughened.
In the specification and claims, “comminuted” is intended to mean reduced to pieces. “Piece” and “pieces” are intended to mean any fiber, strip, ribbon, sliver, filament, shred, bit, fragment, part, flake, slice, cut, chunk, or other portion of solid or solid-like material. “Comminuted” is not intended to imply any particular means of producing the pieces. No particular shape is intended to be implied by the use of the word “comminuted” unless otherwise expressly limited; the pieces can comprise a variety of two and three dimensional shapes of material. Moreover, unless a specific size of material is specified, the use of the term “comminuted” is not intended to imply any particular size of pieces.
“Bioactive agents” include one or more of the following: chemotactic agents; therapeutic agents (e.g. antibiotics, steroidal and non-steroidal analgesics and anti-inflammatories, anti-rejection agents such as immunosuppressants and anti-cancer drugs); various proteins (e.g. short chain peptides, bone morphogenic proteins, glycoprotein and lipoprotein); cell attachment mediators; biologically active ligands; integrin binding sequence; ligands; various growth and/or differentiation agents (e.g. epidermal growth factor, IGF-I, IGF-II, TGF-β I-III, growth and differentiation factors, vascular endothelial growth factors, fibroblast growth factors, platelet derived growth factors, insulin derived growth factor and transforming growth factors, parathyroid hormone, parathyroid hormone related peptide, bFGF; TGF62 superfamily factors; BMP-2; BMP-4; BMP-6; BMP-12; sonic hedgehog; GDF5; GDF6; GDF8; PDGF); small molecules that affect the upregulation of specific growth factors; tenascin-C; hyaluronic acid; chondroitin sulfate; fibronectin; decorin; thromboelastin; thrombin-derived peptides; heparin-binding domains; heparin; heparan sulfate; DNA fragments and DNA plasmids. If other such substances have therapeutic value in the orthopaedic field, it is anticipated that at least some of these substances will have use in the present invention, and such substances should be included in the meaning of “bioactive agent” and “bioactive agents” unless expressly limited otherwise.
“Biologically derived agents” include one or more of the following: bone (autograft, allograft, and xenograft) and derivates of bone; cartilage (autograft, allograft, and xenograft), including, for example, meniscal tissue, and derivatives; ligament (autograft, allograft, and xenograft) and derivatives; derivatives of intestinal tissue (autograft, allograft, and xenograft), including for example submucosa; derivatives of stomach tissue (autograft, allograft, and xenograft), including for example submucosa; derivatives of bladder tissue (autograft, allograft, and xenograft), including for example submucosa; derivatives of alimentary tissue (autograft, allograft, and xenograft), including for example submucosa; derivatives of respiratory tissue (autograft, allograft, and xenograft), including for example submucosa; derivatives of genital tissue (autograft, allograft, and xenograft), including for example submucosa; derivatives of liver tissue (autograft, allograft, and xenograft), including for example liver basement membrane; derivatives of skin (autograft, allograft, and xenograft); platelet rich plasma (PRP), platelet poor plasma, bone marrow aspirate, demineralized bone matrix, insulin derived growth factor, whole blood, fibrin and blood clot. Purified ECM and other collagen sources are also intended to be included within “biologically derived agents.” If other such substances have therapeutic value in the orthopaedic field, it is anticipated that at least some of these substances will have use in the present invention, and such substances should be included in the meaning of “biologically-derived agent” and “biologically-derived agents” unless expressly limited otherwise.
“Biologically derived agents” also include bioremodelable collageneous tissue matrices. The expressions “bioremodelable collagenous tissue matrix” and “naturally occurring bioremodelable collageneous tissue matrix” include matrices derived from native tissue selected from the group consisting of skin, artery, vein, pericardium, heart valve, dura mater, ligament, bone, cartilage, bladder, liver, stomach, fascia and intestine, tendon, whatever the source. Although “naturally occurring bioremodelable collageneous tissue matrix” is intended to refer to matrix material that has been cleaned, processed, sterilized, and optionally crosslinked, it is not within the definition of a naturally occurring bioremodelable collageneous tissue matrix to purify the natural fibers and reform a matrix material from purified natural fibers. The term “bioremodelable collageneous tissue matrices” includes “extracellular matrices” within its definition.
“Cells” include one or more of the following: chondrocytes; fibrochondrocytes; osteocytes; osteoblasts; osteoclasts; synoviocytes; bone marrow cells; mesenchymal cells; stromal cells; stem cells; embryonic stem cells; precursor cells derived from adipose tissue; peripheral blood progenitor cells; stem cells isolated from adult tissue; genetically transformed cells; a combination of chondrocytes and other cells; a combination of osteocytes and other cells; a combination of synoviocytes and other cells; a combination of bone marrow cells and other cells; a combination of mesenchymal cells and other cells; a combination of stromal cells and other cells; a combination of stem cells and other cells; a combination of embryonic stem cells and other cells; a combination of precursor cells isolated from adult tissue and other cells; a combination of peripheral blood progenitor cells and other cells; a combination of stem cells isolated from adult tissue and other cells; and a combination of genetically transformed cells and other cells. If other cells are found to have therapeutic value in the orthopaedic field, it is anticipated that at least some of these cells will have use in the present invention, and such cells should be included within the meaning of “cell” and “cells” unless expressly limited otherwise. Illustratively, in one example of embodiments that are to be seeded with living cells such as chondrocytes, a sterilized implant may be subsequently seeded with living cells and packaged in an appropriate medium for the cell type used. For example, a cell culture medium comprising Dulbecco's Modified Eagles Medium (DMEM) can be used with standard additives such as non-essential amino acids, glucose, ascorbic acid, sodium pyruvate, fungicides, antibiotics, etc., in concentrations deemed appropriate for cell type, shipping conditions, etc.
“Biological lubricants” include: hyaluronic acid and its salts, such as sodium hyaluronate; glycosaminoglycans such as dermatan sulfate, heparan sulfate, chondroiton sulfate and keratan sulfate; synovial fluid and components of synovial fluid, including as mucinous glycoproteins (e.g. lubricin), tribonectins, articular cartilage superficial zone proteins, surface-active phospholipids, lubricating glycoproteins I, II; vitronectin, and rooster comb hyaluronate. “Biological lubricant” is also intended to include commercial products such as ARTHREASE™ high molecular weight sodium hyaluronate, available in Europe from DePuy International, Ltd. of Leeds, England, and manufactured by Bio-Technology General (Israel) Ltd., of Rehovot, Israel; SYNVISC® Hylan G-F 20, manufactured by Biomatrix, Inc., of Ridgefield, N.J. and distributed by Wyeth-Ayerst Pharmaceuticals of Philadelphia, Pa.; HYLAGAN® sodium hyaluronate, available from Sanofi-Synthelabo, Inc., of New York, N.Y., manufactured by FIDIA S.p.A., of Padua, Italy; and HEALON® sodium hyaluronate, available from Pharmacia Corporation of Peapack, N.J. in concentrations of 1%, 1.4% and 2.3% (for opthalmologic uses). If other such substances have therapeutic value in the orthopaedic field, it is anticipated that at least some of these substances will have use in the present invention, and such substances should be included in the meaning of “biological lubricant” and “biological lubricants” unless expressly limited otherwise.
“Biocompatible polymers” is intended to include both synthetic polymers and biopolymers (e.g. collagen). Examples of biocompatible polymers include: polyesters of [alpha]-hydroxycarboxylic acids, such as poly(L-lactide) (PLLA) and polyglycolide (PGA); poly-p-dioxanone (PDS); polycaprolactone (PCL); polyvinyl alcohol (PVA); polyethylene oxide (PEO); polymers disclosed in U.S. Pat. Nos. 6,333,029 and 6,355,699; and any other bioresorbable and biocompatible polymer, co-polymer or mixture of polymers or co-polymers that are utilized in the construction of prosthetic implants. In addition, as new biocompatible, bioresorbable materials are developed, it is expected that at least some of them will be useful materials from which portions of the devices may be made. It should be understood that the above materials are identified by way of example only, and the present disclosure is not limited to any particular material unless expressly called for in the claims.
“Biocompatible inorganic materials” include materials such as hydroxyapatite, all calcium phosphates, alpha-tricalcium phosphate, beta-tricalcium phosphate, calcium carbonate, barium carbonate, calcium sulfate, barium sulfate, polymorphs of calcium phosphates, sintered and non-sintered ceramic particles and combinations of such materials. If other such substances have therapeutic value in the orthopaedic field, it is anticipated that at least some of these substances will have use in the present invention, and such substances should be included in the meaning of “biocompatible inorganic material” and “biocompatible inorganic materials” unless expressly limited otherwise.
It is expected that various combinations of bioactive agents, biologically derived agents, cells, biological lubricants, biocompatible inorganic materials, biocompatible polymers can be used with the scaffolds of the present invention. Various techniques may be used to fix the devices of the present invention. Examples of suitable devices and methods are disclosed in U.S. Patent Application “Unitary Surgical Device and Method”, filed concurrently herewith and incorporated by reference herein in its entirety. Reference is also made to the following applications for filed concurrently herewith and incorporated by reference herein: U.S. patent application Ser. No. 10/195,719 entitled “Devices from Naturally Occurring Biologically Derived Materials”; and U.S. Patent Application Serial No. “Cartilage Repair Apparatus and Method”). To facilitate fixation of the devices to surrounding tissue, the lower cover or the upper cover may be extended. In some cases, the extension of the lower cover or upper cover will be provided with tacks to facilitate the attachment of the device to surrounding tissues. One or more of the layers of the material forming the upper cover or the lower cover may be formed to provide tabs extending away from the device to facilitate attachment of the device to the surrounding tissue.
A repair device may be made in accordance with the present invention in a form such that it can be pulled into, or otherwise placed within, the faces of a tear in a meniscus to extend along the tear. The device comprises strips of naturally occurring ECM material laminated together to form a body portion and at least one extension portion extending away from the body portion. The body portion is shaped to be pulled by the extension portion into the tear to extend along and fill the tear. This body portion may comprise a mass of comminuted naturally occurring ECM captured between the strips to serve as a framework for closing or regenerating the tear. The body portion may be divided into a series of compartments which may be pulled into a tear with a space between each compartment such that the surgeon may trim the device between the compartments.
Thus, one aspect of this disclosure is a device for regenerating a meniscus or a portion thereof, the device comprising a wedge-shaped body having an upper panel and a lower panel angularly separated to define an apex portion and a base portion, the panels being formed of a naturally occurring extracellular matrix.
Another aspect of this disclosure is a device for regenerating a knee meniscus or a portion thereof, the device comprising a wedge-shaped body formed from a naturally occurring extracellular matrix having an apex portion and a base portion spaced radially outwardly from the apex portion, the body providing an upper surface to face a condyle of a femur of the knee and provide an articulation surface therefor and a lower surface to face a tibial platform of the knee, the body providing a plurality of channels disposed between the upper and lower surfaces.
Yet another aspect of this disclosure is a device for regenerating a meniscus of a knee or a portion thereof, the device comprising a shell made from a toughened naturally occurring extracellular matrix and a biologic material to provide a framework for meniscus regeneration disposed in the shell.
Still another aspect of this disclosure is a device for regenerating the meniscus of a knee or a part thereof, the device comprising a plurality of layers of naturally occurring extracellular matrix material laminated together and formed in the shape of a meniscus with an outer radial portion, an inner radial portion and opposite end portions, one or more of the layers being formed to provide a plurality of tabs extending away from the device to be attached to the surrounding tissue of the knee to attach the device.
A further aspect of this disclosure is an implant for regenerating a meniscus or portions of a meniscus on a tibial platform to serve as a support bearing for a condyle above the platform, the implant comprising an outer cover formed from sheets of a naturally occurring extracellular matrix material layered together and formed and toughened by dehydrothermal cross-linking to provide a bearing surface to withstand the forces generated by articulation of the condyle relative to the platform and a biological material below the cover to provide a framework for regenerating the meniscus.
Another aspect of this disclosure is an implant for regenerating a portion of a meniscus in the knee, the implant comprising an outer cover providing a cavity, an upper surface to face the femur of the knee and a lower surface to face the tibial platform of the knee, the cavity being disposed between the surfaces of the cover, the outer cover being formed from a material selected from the group consisting of SIS, stomach submucosa, bladder submucosa, alimentary submucosa, respiratory submucosa, genital submucosa, and liver basement membrane, the upper surface being toughened by cross-linking the collagen fibers, and the cavity being filled with a material selected from the group consisting of blood clots, fibrin, comminuted ECMs and PRP.
An additional aspect of this disclosure is an implant for regenerating a portion of a meniscus in a knee, the implant having a radially outer portion, a radially inner portion, an upper surface and a lower surface, the outer and inner portions being curved to conform to the outer and inner portions, respectively, of the portion of the meniscus to be regenerated, the implant having an outer shell defining the outer and inner portions and upper and lower surfaces, the outer shell being formed from naturally occurring extracellular matrix material, and at least the upper surface being toughened, the shell having a space therein, and a biological material disposed in the space to provide a framework for regenerating the meniscus.
A further aspect of this disclosure is an implant for regenerating a knee meniscus or a portion thereof, the implant having radially outer and inner portions corresponding to the radially outer and inner portions of the portion of the meniscus to be regenerated, and an outer shell providing an inner space extending from the outer portion to the inner portion, the outer shell having an upper surface to be engaged by the femur of the knee and a lower surface to be supported on the tibial platform of the knee, the outer shell being formed from a plurality of layers of SIS laminated together and treated to be toughened to withstand the shearing and compressive forces in the knee in vivo, and at least one material selected from the group consisting of fibrin, blood clots, comminuted SIS and PRP disposed in the space to accommodate the meniscus regeneration.
In another aspect of this disclosure a method is provided for regenerating a portion of a knee meniscus having a radially outer portion and a radially inner portion, the meniscus portion extending circumferentially about a medial or a lateral portion of the tibial platform of the knee, the method comprising the steps of: removing a segment of a meniscus to provide a meniscal space extending circumferentially about a predetermined portion of the tibial platform and leaving remaining segments of the original meniscus, the meniscal space having a radially outer portion and a radially inner portion, providing an implant device constructed from a naturally occurring extracellular matrix to conform to the meniscal space and placing the device into the space, the device having a radially outer portion and a radially inner portion, attaching the device to the adjacent tissue of the knee, and encouraging in regeneration from the radially outer portion of the device to the radially inner portion of the device.
In yet another aspect of this disclosure a method is provided for regenerating a meniscus or a portion thereof comprising the steps of: replacing a portion of an original meniscus with a naturally occurring extracellular matrix material shaped to conform to the meniscus portion removed, and shaping the material such that in vivo the material defines channels extending from the radially outer portion of the meniscus to the radially inner portion of the meniscus to support the regeneration.
In a further aspect of this disclosure a method is provided for regenerating a knee meniscus or a portion thereof comprising the steps of: replacing a portion of an original meniscus with a naturally occurring extracellular matrix material shaped and formed to provide an upper surface toughened to withstand the compression and shear stress of articulation of the knee and an interior space into which meniscal regeneration occurs, and attaching the material to the surrounding tissue.
Still another aspect of this disclosure is a device for regenerating a removed portion of a knee meniscus, the device comprising a shell shaped conformingly to fit into the space occupied by the removed meniscus portion, the shell providing an upper surface to withstand the articulation of the knee and a space under the upper surface, and a biologically derived agent, said biologically derived agent comprising a material selected from the group consisting of comminuted naturally occurring extracellular matrix, fibrin, blood clot and platelet rich plasma (PRP) disposed within the space.
Yet another aspect of this disclosure is a composite device for insertion into a space in a knee meniscus from which space a meniscus portion has been removed, the device comprising an upper cover made from a toughened sheet of naturally occurring extracellular matrix (ECM), the cover defining therebelow a space, and a mass comprising comminuted naturally occurring ECM disposed in the space.
Still another aspect of this disclosure is a plug to be inserted into an opening formed in a knee meniscus, the plug comprising a mass of comminuted naturally occurring ECM formed into the shape of a plug.
A further aspect of this disclosure is a device for repairing a tear in a knee meniscus, the device comprising strips of naturally occurring extracellular matrix laminated together to form a body portion and at least one extension portion extending away from the body portion, the body portion being shaped to be pulled by the extension portion into the tear to extend along and fill the tear.
Moreover, an additional aspect of this disclosure is a device for regenerating a meniscus or a portion thereof, the device comprising a wedge-shaped body having an upper panel and a lower panel angularly separated to define an apex portion and a base portion, the panels being formed of a naturally occurring extracellular matrix, and a support structure disposed between the upper panel and lower panel, the support structure comprising one or more members of rigid and hardened naturally occurring extracellular matrix.
One more aspect of this disclosure is an implantable device for repairing or regenerating at least a portion of a meniscus of a knee, the device comprising a toughened laminate including layers of ECM, the layers of ECM being toughened by a method selected from the group consisting of: compressing the layers of ECM together with heat to form the toughened laminate; compressing the layers of ECM together with vacuum to form the toughened laminate; compressing the layers of ECM together with pressure to form the toughened laminate; mechanically pressing the layers of ECM together while heating the layers to form the toughened laminate; and cross-linking the ECM laminate.
Still another aspect of this disclosure is an implantable device for repairing or regenerating at least a portion of a meniscus of a knee, the device comprising a toughened outer surface and a mass of biological material to provide a framework for meniscus regeneration, at least part of the mass of biological material being covered by the toughened outer surface.
Yet another aspect of this disclosure is an implantable device for repairing or regenerating at least a portion of a meniscus of a knee, the device comprising a wedge-shaped body having an upper panel and a lower panel angularly separated to define an apex portion and a base portion, at least part of the device comprising naturally occurring ECM.
In an additional aspect of this disclosure an implantable device is provided for regenerating at least a portion of a meniscus of a knee, the device comprising a cover sheet and a mass of biological material, the cover sheet extending over and beyond the mass of biological material.
Yet another aspect of this disclosure is an implantable device for regenerating at least a portion of a meniscus of a knee, the device comprising a plurality of surfaces defining compartments, a mass of biological material in each compartment, and a cover extending over the compartments and masses of biological material.
Still another aspect of this disclosure is an implantable device for regenerating at least a portion of a meniscus of a knee, the device comprising at least two adjacent materials having different densities, wherein each of the materials comprises ECM, wherein at least one of the material is treated to increase its density.
An additional aspect of this disclosure is an implantable device for repairing or regenerating at least a portion of vertebrate tissue, the device comprising a sheet of naturally occurring ECM having a density of at least 0.9 gm/cm3.
One more aspect of this disclosure is an implantable device for repairing or regenerating at least a portion of a meniscus of a knee, the device comprising a toughened laminate including layers of naturally occurring bioremodelable collageneous matrix, the laminate being toughened by a method selected from the group consisting of: compressing the layers of naturally occurring bioremodelable collageneous matrix together with heat to form the toughened laminate; compressing the layers of naturally occurring bioremodelable collageneous matrix together with vacuum to form the toughened laminate; compressing the layers of naturally occurring bioremodelable collageneous matrix together with pressure to form the toughened laminate; mechanically pressing the layers of naturally occurring bioremodelable collageneous matrix together while heating the layers to form the toughened laminate; and cross-linking the naturally occurring bioremodelable collageneous matrix laminate.
A final aspect of this disclosure is an implantable device for repairing or regenerating at least a portion of vertebrate tissue, the device comprising a sheet of naturally occurring bioremodelable collageneous matrix toughened to have a density of at least 0.9 gm/cm3.
The above and other features of the present disclosure will become apparent from the following description and the attached drawings.